The relationship of age, sex, and glomerular location to the development of spontaneous lesions in the canine kidney: analysis of a life-span study.

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It is well documented that the presence of spontaneous renal disease and renal dysfunction increases with age in many species of mammals. Such alterations in renal structure and function may significantly affect the interpretation of long-term toxicology studies. The purpose of the present study was to assess the temporal evolution of selected renal lesions (cysts, interstitial inflammation, interstitial fibrosis, and glomerulosclerosis) in laboratory Beagle dogs, an important animal model in chronic toxicology studies. We examined representative sections of the kidneys from 159 purpose-bred and laboratory housed Beagle dogs and analyzed the extent and distribution of spontaneous lesions using the World Health Organization classification system for renal lesions. All dogs examined had renal lesions of varying severities. In the youngest dogs (up to 2 years of age), the density and severity of lesions were minimal, but were more severe by middle age (defined as 3-7 years). The density and severity of interstitial fibrosis and inflammation progressed with advancing age (p < 0.0001 for both) in both sexes. The density of tubular cysts increased linearly with advancing age in females (p = 0.0006), but not in males (p = 0.49). The cortical distribution of glomeruli and advancing age of dogs were significantly related to the development of glomerulosclerosis. As age increased, the presence of glomerulosclerosis increased (p = 0.0008). These data indicate that the development of renal lesions is progressive over the lifetime of a genetically similar population of laboratory Beagle dogs maintained under optimal standard environmental conditions. This information may be useful in the interpretation of compound effects during chronic toxicology studies in the dog.